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Abstract: TH-PO250

Glomerular Permselectivity Associates With Higher Risk of Kidney Failure and Death in Type 2 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Saulnier, Pierre Jean, National Institute of Diabetes and Digestive and Kidney Diseases, Chronic Kidney Disease Section, Phoenix, Arizona, United States
  • Looker, Helen C., National Institute of Diabetes and Digestive and Kidney Diseases, Chronic Kidney Disease Section, Phoenix, Arizona, United States
  • Layton, Anita T., University of Waterloo, Waterloo, Ontario, Canada
  • Lemley, Kevin V., University of Southern California, Los Angeles, California, United States
  • Nelson, Robert G., National Institute of Diabetes and Digestive and Kidney Diseases, Chronic Kidney Disease Section, Phoenix, Arizona, United States
  • Bjornstad, Petter, University of Colorado, Aurora, Colorado, United States
Background

Hydrodynamic models of hindered solute transport are used to characterize the size selective properties of the glomerular barrier. One model assumes the glomerular capillary is perforated by restrictive cylindrical pores of identical pore radius and a parallel shunt pathway of nonrestrictive pores characterized by a parameter, ωo, that estimates the fraction of total filtrate passing through the shunt. We reported previously that type 2 diabetes (T2D) associated with an increase in ωo. Here we examine whether ωo associates with incident kidney failure or death in Pima Indians with T2D.

Methods

Iothalamate GFR and fractional clearance of dextrans of graded sizes were measured in 185 adults (74 men, 111 women) with T2D. ωo was computed from the dextran sieving data. Hazard ratios (HR) for kidney failure or death were expressed per 1 standard deviation (SD) increase of ωo by Cox regression after adjusting for age, sex, GFR, ACR, HbA1c and mean arterial blood pressure (MAP).

Results

At baseline, mean age (±SD) was 43±10 years, diabetes duration 8.8±8.7 years, HbA1c 8.9±2.4%, MAP 93±12 mm Hg, GFR 147±46 ml/min, and median (IQR) ACR was 41 (10-229) mg/g. During a median follow-up of 29 years, 70 participants developed kidney failure and 134 died, 60 after developing kidney failure. Baseline ωowas higher in participants who developed kidney failure (0.00262 ± 0.00095 vs 0.00204 ±0.00077, P=0.0016) or died (0.00240 ± 0.00086 vs 0.00188 ± 0.00097, P=0.015). After adjustment, each 1 SD increase in baseline ωo associated with increased risk of kidney failure (HR: 1.60, 95% CI 1.20-2.14) and death (HR: 1.34, 95% CI 1.06-1.68) [Table].

Conclusion

Enhanced transglomerular passage of test macromolecules associated with kidney failure and death, independent of albuminuria and GFR, suggesting that mechanisms responsible for impaired glomerular barrier size selectivity are important determinants of adverse health outcomes in T2D.

Hazard ratio for kidney failure and death according to baseline shunt coefficient (ωo)
  Kidney failure
70 events/185
 Death
134 events/185
 
  HR (95%CI)P-valueHR (95%CI)P-value
Shunt coefficient (ωo) per 1 SDCrude2.00 (1.55-2.57)<0.00011.50 (1.25-1.81)<0.0001
Shunt coefficient (ωo) per 1 SDAdjusted*1.60 (1.20-2.14)0.00161.34 (1.06-1.68)<0.0001

*adjusted for age sex GFR ACR HbA1c and MAP

Funding

  • NIDDK Support